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Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3.
Florian, Rahel T; Kraft, Florian; Leitão, Elsa; Kaya, Sabine; Klebe, Stephan; Magnin, Eloi; van Rootselaar, Anne-Fleur; Buratti, Julien; Kühnel, Theresa; Schröder, Christopher; Giesselmann, Sebastian; Tschernoster, Nikolai; Altmueller, Janine; Lamiral, Anaide; Keren, Boris; Nava, Caroline; Bouteiller, Delphine; Forlani, Sylvie; Jornea, Ludmila; Kubica, Regina; Ye, Tao; Plassard, Damien; Jost, Bernard; Meyer, Vincent; Deleuze, Jean-François; Delpu, Yannick; Avarello, Mario D M; Vijfhuizen, Lisanne S; Rudolf, Gabrielle; Hirsch, Edouard; Kroes, Thessa; Reif, Philipp S; Rosenow, Felix; Ganos, Christos; Vidailhet, Marie; Thivard, Lionel; Mathieu, Alexandre; Bourgeron, Thomas; Kurth, Ingo; Rafehi, Haloom; Steenpass, Laura; Horsthemke, Bernhard; LeGuern, Eric; Klein, Karl Martin; Labauge, Pierre; Bennett, Mark F; Bahlo, Melanie; Gecz, Jozef; Corbett, Mark A; Tijssen, Marina A J.
Afiliação
  • Florian RT; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Kraft F; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany.
  • Leitão E; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Kaya S; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Klebe S; Department of Neurology, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Magnin E; Department of Neurology, CHU Jean Minjoz, 25000, Besançon, France.
  • van Rootselaar AF; Departments of Neurology and Clinical Neurophysiology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
  • Buratti J; AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
  • Kühnel T; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Schröder C; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Giesselmann S; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany.
  • Tschernoster N; Cologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Weyertal 115b, 50931, Cologne, Germany.
  • Altmueller J; Cologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Weyertal 115b, 50931, Cologne, Germany.
  • Lamiral A; Department of Neurology, CHU Jean Minjoz, 25000, Besançon, France.
  • Keren B; AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
  • Nava C; AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
  • Bouteiller D; Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
  • Forlani S; Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
  • Jornea L; Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
  • Kubica R; Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
  • Ye T; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Plassard D; IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
  • Jost B; IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
  • Meyer V; IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
  • Deleuze JF; Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France.
  • Delpu Y; Centre National de Recherche en Génomique Humaine (CNRGH), Institut de Biologie François Jacob, CEA, Université Paris-Saclay, F-91057, Evry, France.
  • Avarello MDM; Genomic Vision, 80 Rue des Meuniers, 92220, Bagneux, France.
  • Vijfhuizen LS; Genomic Vision, 80 Rue des Meuniers, 92220, Bagneux, France.
  • Rudolf G; Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333, ZA, Leiden, The Netherlands.
  • Hirsch E; IGBMC, CNRS UMR 7104/INSERM U1258/Université de Strasbourg, 1 Rue Laurent Fries, 67400, Illkirch-Graffenstaden, France.
  • Kroes T; Department of Neurology-centre de référence des epilepsies rares, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France.
  • Reif PS; Department of Neurology-centre de référence des epilepsies rares, University Hospital of Strasbourg, 1 Avenue Molière, 67200, Strasbourg, France.
  • Rosenow F; School of Biological Sciences, School of Medicine and Robinson Research Institute, The University of Adelaide, Adelaide, 5005, SA, Australia.
  • Ganos C; Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), 60323, Frankfurt am Main, Germany.
  • Vidailhet M; Department of Neurology, Epilepsy Center Hessen, Philipps University, 35037, Marburg, Germany.
  • Thivard L; Epilepsy Center Frankfurt Rhine-Main, Department of Neurology, Goethe University and LOEWE Center for Personalized Translational Epilepsy Research (CePTER), 60323, Frankfurt am Main, Germany.
  • Mathieu A; Department of Neurology, Epilepsy Center Hessen, Philipps University, 35037, Marburg, Germany.
  • Bourgeron T; Department of Neurology, Charité University Medicine Berlin, 10117, Berlin, Germany.
  • Kurth I; Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France.
  • Rafehi H; APHP, Hôpital Pitié-Salpêtrière, Département de Neurologie, 75013, Paris, France.
  • Steenpass L; APHP, Hôpital Pitié-Salpêtrière, Département de Neurologie, 75013, Paris, France.
  • Horsthemke B; Human Genetics and Cognitive Functions, Pasteur Institute, UMR3571 CNRS, Université de Paris, 75015, Paris, France.
  • LeGuern E; Institute of Human Genetics, Medical Faculty, RWTH Aachen University, 52062, Aachen, Germany.
  • Klein KM; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, VIC, Australia.
  • Labauge P; Department of Medical Biology, University of Melbourne, Melbourne, 3010, VIC, Australia.
  • Bennett MF; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, 3084, VIC, Australia.
  • Bahlo M; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Gecz J; Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
  • Tijssen MAJ; AP-HP, Hôpital Pitié-Salpêtrière, Département de Génétique, 75013, Paris, France.
Nat Commun ; 10(1): 4919, 2019 10 29.
Article em En | MEDLINE | ID: mdl-31664039
ABSTRACT
Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Epilepsias Mioclônicas / Ubiquitina-Proteína Ligases / Expansão das Repetições de DNA / Proteínas de Membrana Tipo de estudo: Risk_factors_studies Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Epilepsias Mioclônicas / Ubiquitina-Proteína Ligases / Expansão das Repetições de DNA / Proteínas de Membrana Tipo de estudo: Risk_factors_studies Limite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article